Table 2.

Odds ratios for joint associations of smoking status (ever vs never smokers) and 12 susceptibility variants with bladder cancer risk

Observed ORs (95%CIs)aExpected OR jointbPinteractionc
Chr location (gene/s in neighboring region)rs number [risk allele]NdCasesControlsRAFeOR SNPOR smokingOR jointAdditiveMult.AdditiveMult.
8p22 (NAT2)rs1495741 [A]83,9275,6620.770.97 (0.81–1.17)2.02 (1.68–2.42)2.48 (2.08–2.96)1.991.966.6 × 10−40.029
1p13.3 (GSTM1)[del]63,6193,9270.711.70 (1.38–2.09)3.30 (2.71–4.03)4.69 (3.86–5.69)4.005.610.0080.126
8q24.21 (MYC)rs9642880 [T]53,3925,1030.451.31 (1.05–1.64)2.73 (2.17–3.44)3.49 (2.80–4.35)3.043.580.0350.850
3q28 (TP63)rs710521 [A]53,3865,1050.741.37 (0.91–2.06)2.89 (1.84–4.54)3.68 (2.45–5.53)3.263.970.2820.747
8q24.3 (PSCA)rs2294008 [T]63,7105,4330.471.08 (0.88–1.34)2.43 (1.95–3.02)2.90 (2.37–3.56)2.512.630.0330.425
5p15.33 (CLPTM1L)rs401681 [C]53,3935,1120.551.06 (0.82–1.36)2.50 (1.90–3.27)2.87 (2.23–3.70)2.552.630.1260.544
4p16.3 (TMEM129 TACC3-FGFR3)rs798766 [T]83,9295,6630.201.21 (1.00–1.46)2.35 (2.02–2.72)2.72 (2.33–3.18)2.562.840.3270.701
22q13.1 (CBX6, APOBEC3A)rs1014971 [T]83,9325,6380.651.15 (0.86–1.55)2.08 (1.51–2.87)2.71 (2.03–3.64)2.232.400.0360.465
19q12 (CCNE1)rs8102137 [C]83,9345,6630.331.31 (1.09–1.58)2.55 (2.14–3.03)2.85 (2.41–3.38)2.863.350.9610.133
2q37.1 (UGT1A family)rs11892031 [A]83,9285,6550.921.24 (0.95–1.61)2.30 (1.74–3.05)2.89 (2.23–3.74)2.542.850.1060.934
2q37.1 (UGT1A6)rs17863783 [G]83,9145,2990.971.63 (0.95–2.78)1.92 (1.07–3.46)3.83 (2.24–6.54)2.553.128.8 × 10−40.492
18q12.3 (SLC14A1)rs10775480/rs10853535 [T]83,8835,6350.431.20 (0.98–1.47)2.31 (1.88–2.82)2.84 (2.34–3.44)2.512.770.0530.833

eRAF, risk allele frequency in the control populations. The rs1495741 AA genotype (corresponding to the NAT2 slow acetylation phenotype and with a frequency of 0.60 in controls) was compared with the combined GG and AG genotypes (corresponding to the NAT2 rapid/intermediate acetylation phenotype) (21) in all analyses. The GSTM1 null (−/−) genotype with a frequency of 0.51 was compared with the combined (+/−) and (+/+) genotypes (GSTM1 “present”) in all analyses. The rare homozygous and heterozygous genotypes for rs11892031 (AC/CC) and rs17863783 (GT/TT) were combined and compared with the common homozygous genotypes carrying 2 risk alleles (AA for rs11892031 and GG for rs17863783) for all analyses due to the low frequency of the rare homozygous genotypes.

  • aORs estimated from logistic regression models including main effects for SNP and smoking status (ever, never) and an interaction term for SNP*smoking status, and adjusted for study, age, and gender. ORs for each SNP are for the risk allele, assuming dominant effects.

  • bExpected ORs for the joint association of SNP and smoking status under additive and multiplicative (Mult.) models. The expected ORs under an additive model are calculated as OR SNP+OR smoking-1. The expected ORs under a multiplicative model are calculated as OR SNP*OR smoking

  • cP values from 1df tests for additive and multiplicative (Mult.) interactions between smoking status and SNP. P < 0.05 are bolded.

  • dN denotes the number of studies included in analyses (NEBCS-ME, VT and NEBCS-NH are counted as one study). GSTM1 and rs2294008 data missing in NHS and HPFS. rs9642880, rs710521, rs401681 data missing in NEBCS (NH), NHS, and HPFS. Differences in the number of cases and controls in each study and the total number of cases and controls in Supplementary Table S1 are due to missing genotype or smoking information (see Materials and Methods for details).